Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells.

Constitutional heterozygous pathogenic variants in the exonuclease domain of POLE and POLD1, which affect the proofreading activity of the corresponding polymerases, cause a cancer predisposition syndrome characterized by increased risk of gastrointestinal polyposis, colorectal cancer, endometrial cancer and other tumor types. The generally accepted explanation for the connection between the disruption of the proofreading activity of polymerases epsilon and delta and cancer development is through an increase in the somatic mutation rate. Here we studied an extended family with multiple members heterozygous for the pathogenic POLD1 variant c.1421T>C p.(Leu474Pro), which segregates with the polyposis and cancer phenotypes. Through the analysis of mutational patterns of patient-derived fibroblasts colonies and de novo mutations obtained by parent-offspring comparisons, we concluded that heterozygous POLD1 L474P just subtly increases the somatic and germline mutation burden. In contrast, tumors developed in individuals with a heterozygous mutation in the exonuclease domain of POLD1, including L474P, have an extremely high mutation rate (>100 mut/Mb) associated with signature SBS10d. We solved this contradiction through the observation that tumorigenesis involves somatic inactivation of the wildtype POLD1 allele. These results imply that exonuclease deficiency of polymerase delta has a recessive effect on mutation rate.

Trunk Injection of Citrus Trees with a Polymeric Nanobactericide Reduces Huanglongbing Severity Caused by Candidatus Liberibacter asiaticus.

Huanglongbing (HLB) is a disease caused by the phloem- limited Candidatus Liberibacter asiaticus (CLas) that affects the citrus industry worldwide. To date, only indirect strategies have been implemented to eradicate HLB. Included among these is the population control of the psyllid vector (Diaphorina citri), which usually provides inconsistent results. Even though strategies for direct CLas suppression seem a priori more promising, only a handful of reports have been focused on a confrontation of the pathogen. Recent developments in polymer chemistry have allowed the design of polycationic self-assembled block copolymers with outstanding antibacterial capabilities. Here, we report the use of polymeric nano-sized bactericide particles (PNB) to control CLas directly in the phloem vasculature. The field experiments were performed in Rioverde, San Luis Potosí, and is one of the most important citrusproducing regions in Mexico. An average 52% reduction in the bacterial population was produced when PNB was injected directly into the trunk of 20 infected trees, although, in some cases, reduction levels reached 97%. These results position PNB as a novel and promising nanotechnological tool for citrus crop protection against CLas and other related pathogens.

Evaluation of the Stability of Newborn Hospital Parenteral Nutrition Solutions.

(1) Background: parenteral nutrition (PN) solutions are an extremely complex mixture. It is composed of a multitude of chemical elements that can give rise to a large number of interactions that condition its stability and safety. The aim of this study was to evaluate the stability of PN solutions for preterm infants. (2) Methods: eight samples were prepared according to the protocol for prescribing PN in preterm infants. Samples PN1-PN7 had the normal progression of macronutrients and standard amounts of micronutrients for a 1 kg preterm infant. The PN8 sample had a high concentration of electrolytes, with the idea of forcing stability limits. Samples were stored both at room temperature and under refrigeration. Measurements of globule size, pH, density, and viscosity were performed in both storage protocols on different days after processing. (3) Results: the changes in the composition of the samples did not affect the evolution of the stability at the different measurement times and temperatures. Viscosity was affected by the compositional changes made in the PN samples, but no alterations due to time or temperature were observed. Density and pH remained stable, without significant changes due to time, storage temperature, or different composition. (4) Conclusion: all samples remained stable during the study period and did not undergo significant alterations due to compositional changes or different experimental conditions.

ESSENCE-Dock: A Consensus-Based Approach to Enhance Virtual Screening Enrichment in Drug Discovery.

Drug development is a complex, costly, and time-consuming endeavor. While high-throughput screening (HTS) plays a critical role in the discovery stage, it is one of many factors contributing to these challenges. In certain contexts, virtual screening can complement the HTS, potentially offering a more streamlined approach in the initial stages of drug discovery. Molecular docking is an example of a popular virtual screening technique that is often used for this purpose; however, its effectiveness can vary greatly. This has led to the use of consensus docking approaches that combine results from different docking methods to improve the identification of active compounds and reduce the occurrence of false positives. However, many of these methods do not fully leverage the latest advancements in molecular docking. In response, we present ESSENCE-Dock (Effective Structural Screening ENrichment ConsEnsus Dock), a new consensus docking workflow aimed at decreasing false positives and increasing the discovery of active compounds. By utilizing a combination of novel docking algorithms, we improve the selection process for potential active compounds. ESSENCE-Dock has been made to be user-friendly, requiring only a few simple commands to perform a complete screening while also being designed for use in high-performance computing (HPC) environments.

The In Vitro Inhibitory Activity of Pacaya Palm Rachis versus Dipeptidyl Peptidase-IV, Angiotensin-Converting Enzyme, α-Glucosidase and α-Amylase.

The pacaya palm (Chamaedorea tepejilote Liebm) is an important food that is commonly consumed in Mexico and Central America due to its nutritive value. It is also used as a nutraceutical food against some chronic diseases, such as hypertension and hyperglycemia. However, few reports have indicated its possible potential. For this reason, the goal of this research was to evaluate the effects of the enzymatic activity of the pacaya palm inflorescence rachis on both hypertension and hyperglycemia and the effects of thermal treatments on the enzymatic activity. The enzymatic inhibition of ACE (angiotensin-converting enzyme), DPP-IV (dipeptidyl peptidase-IV), α-glucosidase and α-amylase were evaluated, all with powder extracts of pacaya palm inflorescences rachis. The results indicated that thermally treated rachis showed increased enzymatic inhibitory activity against α-amylase and DPP-IV. However, all rachis, both with and without thermal treatment, showed low- or no enzymatic activity against α-glucosidase and ACE. Apparently, the mechanism of action of the antidiabetic effect of rachis is mediated by the inhibition of α-amylase and DPP-IV and does not contribute with a significant effect on enzymes involved in the hypertension mechanism. Finally, the properties of the extract were modified via the extraction method and the temperature tested.

Factors associated with longer survival among older medicare patients after diagnosis of supratentorial primary brain malignancies: a retrospective cohort study.

OBJECTIVES: Despite recent advances, the prognosis for primary malignant brain tumors (PMBTs) remains poor. Some commonly prescribed medications may exhibit anti-tumor properties in various cancers, and neurodegenerative diseases may activate pathways that counteract gliomagenesis. Our study is focused on determining if there is a correlation between the use of metformin, beta-blockers, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), or the presence of Parkinson's disease (PD), and the survival rates following a diagnosis of a PMBT. METHODS: This analysis of the 100% Texas Medicare Database identified patients aged 66+ years diagnosed with a supratentorial PMBT from 2014-2017. Cox proportional hazards regression was employed to analyze survival following diagnosis and associations of survival with surgical intervention, radiation, PD diagnosis, and prescription of metformin, beta-blockers, ACEIs, or ARBs. RESULTS: There were 1,943 patients who met study criteria, and the median age was 74 years. When medication utilization was stratified by none, pre-diagnosis only, post-diagnosis only, or both pre- and post-diagnosis (continuous), continuous utilization of metformin, beta-blockers, ACEIs, or ARBs was associated with prolonged survival compared to no utilization (hazard ratio [HR]:0.45, 95% CI:0.33-0.62; HR:0.71. 95% CI:0.59-0.86; HR:0.59, 95% CI:0.48-0.72; and HR:0.45, 95% CI:0.35-0.58 respectively). PD was also associated with longer survival (HR:0.59-0.63 across the four models). DISCUSSION: Our study suggests that metformin, beta-blockers, ACEIs, ARBs, and comorbid PD are associated with a survival benefit among geriatric Medicare patients with supratentorial PMBTs.

Preferences and Demand for Mosquito Control among Dengue-Endemic Communities in Peñuelas, Puerto Rico: An Application of the Best-Worst Choice Model.

Aedes aegypti is the primary vector of dengue virus and threatens 3.9 billion people living in many tropical and subtropical countries. Prevention and reduction of dengue and other Aedes-borne viruses, including Zika and chikungunya, requires control of mosquito populations. Community mobilization and input are essential components of vector control efforts. Many vector control campaigns do not engage communities prior to implementation, leading to program failure. Those that do often conduct basic knowledge, attitude, and practice surveys that are not designed to explicitly elicit preferences. Here, we applied a novel stated preference elicitation tool, best-worst choice, to understand preferences, willingness to participate, and willingness to pay for mosquito control in dengue-endemic communities of Peñuelas, Puerto Rico. Findings revealed that the community preferred mosquito control programs that are 1) applied at the neighborhood level, 2) implemented by the local government, and 3) focused specifically on reducing disease transmission (e.g., dengue) instead of mosquito nuisance. Programs targeting the reduction of disease transmission and higher educational level of participants increased willingness to participate. Participants were willing to pay an average of $72 annually to have a program targeting the reduction of diseases such as dengue. This study serves as a model to engage communities in the design of mosquito control programs and improve stakeholders' decision-making.

"Deficiency in ELF4, X-Linked": a Monogenic Disease Entity Resembling Behçet's Syndrome and Inflammatory Bowel Disease.

Defining monogenic drivers of autoinflammatory syndromes elucidates mechanisms of disease in patients with these inborn errors of immunity and can facilitate targeted therapeutic interventions. Here, we describe a cohort of patients with a Behçet's- and inflammatory bowel disease (IBD)-like disorder termed "deficiency in ELF4, X-linked" (DEX) affecting males with loss-of-function variants in the ELF4 transcription factor gene located on the X chromosome. An international cohort of fourteen DEX patients was assessed to identify unifying clinical manifestations and diagnostic criteria as well as collate findings informing therapeutic responses. DEX patients exhibit a heterogeneous clinical phenotype including weight loss, oral and gastrointestinal aphthous ulcers, fevers, skin inflammation, gastrointestinal symptoms, arthritis, arthralgia, and myalgia, with findings of increased inflammatory markers, anemia, neutrophilic leukocytosis, thrombocytosis, intermittently low natural killer and class-switched memory B cells, and increased inflammatory cytokines in the serum. Patients have been predominantly treated with anti-inflammatory agents, with the majority of DEX patients treated with biologics targeting TNFα.

Characterization of genomic variants associated with congenital heart disease in patients from southwestern Colombian.

Congenital heart diseases correspond to errors during embryogenesis, generating structural and functional malformations. Congenital heart diseases are the most prevalent congenital malformations and are responsible for the highest infant morbidity and mortality. Among these cases, 8 % can be attributed to variants in genes associated with cardiac development. To establish the population frequency of genomic variants that cause congenital heart disease, a review of the scope of prevalent genes was carried out, complete exome sequencing results of 320 patients without suspicion of congenital heart disease were used, the exome sequencing is a technique based on DNA extraction using a Qiagen kit, with massive sequencing of Nextera TM libraries using an Illumina platform with 100X coverage, alignment with reference genome GRCh38/hg19, and analysis with the CRAVAT program; clinical characterization, significance classification, and gene interaction networks were performed. The scope analysis allowed to determine that the genes NKX2-5, TBX20, GATA4, NOTCH1, PTPN11 are the most prevalent, the variants with the highest allelic frequency were c.63A > G (0.2844), c.39T > C (0.3406), c.1132A > G (0.0406), c.1669+9T > C (0.3531) and c.854-30T > C (0.0875) respectively; 4 variants were reclassified by in silico tools, in the NKX2-5 gene c.335-311_335-303del from benign to probably pathogenic, in the NOTCH1 gene c.2354-24C > T from benign to pathogenic, and in the PTPN11 gene c.2354-24C > T and c.854-30T > C from benign to pathogenic. 17 % of intronic variants and 4.8 % of missense variants were identified. This work contributes to knowledge about the frequency with which genomic variants associated with congenital heart disease are present in the population, generating a tool for early diagnosis, early treatment, thus reducing morbidity and mortality, with a view to future universal molecular neonatal screening of congenital heart disease.

Enterobacter sp. DBA51 produces ACC deaminase and promotes the growth of tomato (Solanum lycopersicum L.) and tobacco (Nicotiana tabacum L.) plants under greenhouse condition.

Bacterial isolated from rhizospheric soil associated with the semi-desertic plant Coronilla juncea L. were screened for 1-aminocyclopropane-1-carboxylate deaminase (ACCD) activity, a common trait for plant-growth-promoting rhizobacteria (PGPR). Among bacterial isolates, strain DBA51 showed phosphate solubilizing index (PSI), producing indole acetic acid (IAA), and with the hemolysis-negative test. Sequencing and analysis of the 16S rDNA gene identified DBA51 as Enterobacter. DBA51 did not show antagonistic activity in vitro against bacterial (Clavibacter michiganensis, Pseudomonas syringae pv. tomato DC3000 and Pectobacterium cacticidum FHLGJ22) and fungal phytopathogens (Alternaria sp., Fusarium oxysporum fsp. lycopersici, Fusarium oxysporum fsp. cubense M5, and Rhizoctonia sp.). Root inoculations with DBA51 in tomato (Solanum lycopersicum L.) and tobacco (Nicotiana tabacum L.) plants were performed under greenhouse conditions. Plant height (20 %) and root biomass (40 %) were significantly enhanced in tomato plants inoculated with DBA51 compared to non-inoculated plants, although for tobacco plants, only root biomass (27 %) showed significant differences with DBA51. In addition, physiological parameters such as photosynthetic rate (µmol CO2 m-2 s-1), stomatal conductance (mol H2O m-2 s-1), and transpiration rate (mmol H2O m-2 s-1) were also evaluated, and no differences were detected between DBA51-inoculated and control treatment in tomato and tobacco leaves. The observed results indicate that the DBA51 strain could be used as a biofertilizer to improve yields of horticultural crops.

Associations between day-level affect profiles and same-day substance use among young adults.

OBJECTIVE: Emotions play a critical role in health risk behaviors, including substance use. However, current research often focuses exclusively on average levels of positive and negative affect, neglecting the complexity of daily emotional patterns. By capturing multiple dimensions of affect, including arousal and discrete states, we can improve our understanding of proximal predictors of substance use. The present study demonstrates the utility of a novel methodological approach for assessing affect patterns in daily life in relation to alcohol and cannabis use. METHOD: Daily diary data from N = 154 young adults who reported recent heavy episodic drinking and simultaneous use of alcohol and cannabis were analyzed using a mixed-indicator latent profile analysis to identify and describe day-level affective patterns and outcomes. RESULTS: Results revealed five distinct day-level profiles of affect: undifferentiated negative affect days, undifferentiated positive affect days, high-arousal positive affect days, mixed affect days, and low reactivity days. Undifferentiated positive affect days, high-arousal positive affect days, and low reactivity days were associated with significantly greater odds of same-day alcohol use compared to days characterized by undifferentiated negative affect (χ² = 10.55, p = .032). CONCLUSIONS: Findings suggest that daily affect patterns differentially impact alcohol use and can inform the development of interventions for problematic substance use. Additionally, the innovative methodological approach employed herein could be applicable for investigating the role of emotion in other health behaviors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Genetic and clinical characterization of a novel FH founder mutation in families with hereditary leiomyomatosis and renal cell cancer syndrome.

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer syndrome is a rare autosomal dominant hereditary syndrome. Previously, we published the largest cohort of FH mutation carriers in Spain and observed a highly recurrent missense heterozygous variant, FH(NM_000143.4):c.1118A > G p.(Asn373Ser), in 104 individuals from 31 apparently unrelated families. Here, we aimed to establish its founder effect and characterize the associated clinical phenotype. RESULTS: Haplotype analysis confirmed that families shared a common haplotype (32/38 markers) spanning 0.61-0.82 Mb, indicating this recurrent variant was inherited from a founder ancestor. Cutaneous and uterine leiomyomatosis were diagnosed in 64.6% (64/99) and 98% (50/51) of patients, respectively, and renal cell cancer was present in 10.4% (10/96). The pathogenic FH_c.1118A > G variant is a Spanish founder mutation that originated 12-26 generations ago. We estimate that the variant may have appeared between 1370 and 1720. Individuals carrying this founder mutation had similar frequency of renal cell cancer and a higher frequency of renal cysts and leiomyomas than those in other cohorts of this syndrome. CONCLUSIONS: In the Spanish province of Alicante there is a high prevalence of HLRCC because of the founder mutation FH c.1118A > G; p.(Asn373Ser). The characterization of founder mutations provides accurate and specific information regarding their penetrance and expressivity. In individuals with suspected HLRCC from the province of Alicante, genetic testing by direct analysis of the founder FH c.1118A > G; p.(Asn373Ser) mutation may be a faster and more efficient diagnostic tool compared with complete gene sequencing.

Use of multi-gene panels in patients at high risk of hereditary digestive cancer: position statement of AEG, SEOM, AEGH and IMPaCT-GENÓMICA consortium. / Uso de paneles de genes en pacientes con alto riesgo de cáncer digestivo hereditario: documento de posicionamiento de la AEG, SEOM, AEGH y consorcio IMPaCT-GENÓMICA.

This position statement, sponsored by the Asociación Española de Gastroenterología, the Sociedad Española de Oncología Médica, the Asociación Española de Genética Humana and the IMPaCT-Genómica Consortium aims to establish recommendations for use of multi-gene panel testing in patients at high risk of hereditary gastrointestinal and pancreatic cancer. To rate the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We reached a consensus among experts using a Delphi method. The document includes recommendations on clinical scenarios where multi-gene panel testing is recommended in colorectal cancer, polyposis syndromes, gastric and pancreatic cancer, as well as the genes to be considered in each clinical scenario. Recommendations on the evaluation of mosaicisms, counseling strategies in the absence of an index subject and, finally, constitutional analysis after identification of pathogenic tumor variants are also made.

A Novel Technique for Performing Transfemoral Transcatheter Self-Expanding Aortic Valve Replacement With No Contrast Which Minimizes Acute Kidney Injury.

Transcatheter aortic valve replacement (TAVR) treats severe aortic stenosis. However, patients with limited renal function may be ineligible for contrast use during valve deployment. We evaluate TAVR via transfemoral approach using 2-wire technique and no contrast injection. Primary endpoints are acute kidney injury and procedural success. Safety analysis includes mortality, stroke, myocardial infarction, coronary obstruction, and more. Forty-six patients were included; most with preserved ejection fraction. Baseline creatinine was 1.63 ± 0.68 and post-TAVR was significantly better (1.47 ± 0.64, P < 0.01). No statistical difference existed between creatinine at baseline and 30 days. After TAVR, 91% had no paravalvular leak (PVL). Peak-velocity post-TAVR was 1.32 ± 0.33 and mean-gradient was 7 ± 4. No valve repositioning during deployment was required. No mortality at 30 days without incidence of stroke, myocardial infarction or coronary obstruction. One patient had retroperitoneal bleeding requiring transfusion. The noncontrast technique for self-expanding valve deployment is feasible and safe in patients who cannot tolerate contrast.

Isolated Intramedullary Thoracic Spinal Sarcoidosis: A Case Report and Review of the Literature.

Sarcoidosis is a multisystemic inflammatory granulomatosis disease that rarely involves the central nervous system (CNS) and is even more so rarely isolated to the intramedullary thoracic spine. In isolated CNS sarcoidosis cases, surgical treatment is debated. We present here a case report and literature review on intramedullary thoracic spine sarcoidosis to evaluate potential portents of spine involvement and indications for surgical intervention. A 47-year-old female with a prior history of renal cell carcinoma presented with a week-long history of urinary retention and bilateral lower extremity numbness, and a 24-hour history of left lower extremity (LLE) weakness with saddle anesthesia. Magnetic resonance imaging demonstrated a syrinx spanning the spinal cord to the conus medullaris and a contrast-enhancing, expansile intramedullary thoracic lesion at T6-T7 with a non-enhancing, cystic right paraspinal lesion at T5. Given the patient's history of a kidney neoplasm, a metastatic work-up was completed. Biopsy of the T5 lesion was consistent with endometriosis. The patient underwent a T6-8 laminectomy with excisional biopsy and gross total resection of the intramedullary mass. Initial pathology was notable for lymphohistiocytic infiltrate with coagulative necrosis and rare multinucleated giant cells. At the one-month follow-up, the patient had improving LLE weakness and continued impairment of gait, balance, and coordination, but her symptoms of urinary retention, paresthesia, and numbness were resolved. Final pathology supported a diagnosis of sarcoidosis. At the three-month follow-up, the patient reported intermittent surgical site pain, but no other symptoms. She is followed up by her primary care consultant for symptom management and recurrence monitoring. Apart from the presented case, only one case of isolated intramedullary thoracic spine sarcoidosis was identified in the literature. The only case, of both review and presented, without significant symptom improvement did not undergo surgery. The available literature is limited; however, early surgical intervention may be indicated in isolated thoracic spine sarcoidosis.

Zero to Hero? Reducing the Rate of Acute Kidney Injury in Transcatheter Aortic Valve Replacement: The Low Contrast Approach.

Background: Acute kidney injury (AKI) after transcatheter aortic valve replacement (TAVR) increases hospital stay, morbidity, and mortality, and the amount of contrast used during the procedure has been linked to the occurrence of AKI. Reducing the amount of contrast used during TAVR is hypothesized to decrease AKI without compromising outcomes. Methods: We conducted a single-institution retrospective analysis of patients who underwent TAVR from 2017 to 2019. Patients receiving ≤20 mL of contrast were labeled as group I, and patients receiving >20 mL of contrast were labeled as group II. Primary endpoints were 30-day mortality, AKI, and early aortic regurgitation. Results: A total of 594 patients met the inclusion and exclusion criteria, with 429 patients (72.2%) included in group I and 165 patients (27.8%) included in group II. Two hundred eighteen patients (50.8%) from group I and 41 patients (24.8%) from group II had preoperative chronic kidney disease stage III or IV. The mean contrast volume was 8.5 ± 6 mL for group I and 33 ± 16 mL for group II (P<0.001). In group I, 13 patients (3.0%) developed AKI, and 6 (1.4%) required hemodialysis. In group II, 9 (5.5%) patients developed AKI, and 1 (0.6%) required hemodialysis. The differences between the 2 groups for AKI and hemodialysis were not statistically significant. Overall, 579 patients (97.5%) had less than moderate aortic regurgitation in the postoperative echocardiogram. Conclusion: Low contrast TAVR is safe and effective and can reduce the incidence of AKI when compared to the standard contrast dose without affecting outcomes such as death and aortic regurgitation.

Computing the Relative Affinity of Chlorophylls a and b to Light-Harvesting Complex II.

In plants and algae, the primary antenna protein bound to photosystem II is light-harvesting complex II (LHCII), a pigment-protein complex that binds eight chlorophyll (Chl) a molecules and six Chl b molecules. Chl a and Chl b differ only in that Chl a has a methyl group (-CH3) on one of its pyrrole rings, while Chl b has a formyl group (-CHO) at that position. This blue-shifts the Chl b absorbance relative to Chl a. It is not known how the protein selectively binds the right Chl type at each site. Knowing the selection criteria would allow the design of light-harvesting complexes that bind different Chl types, modifying an organism to utilize the light of different wavelengths. The difference in the binding affinity of Chl a and Chl b in pea and spinach LHCII was calculated using multiconformation continuum electrostatics and free energy perturbation. Both methods have identified some Chl sites where the bound Chl type (a or b) has a significantly higher affinity, especially when the protein provides a hydrogen bond for the Chl b formyl group. However, the Chl a sites often have little calculated preference for one Chl type, so they are predicted to bind a mixture of Chl a and b. The electron density of the spinach LHCII was reanalyzed, which, however, confirmed that there is negligible Chl b in the Chl a-binding sites. It is suggested that the protein chooses the correct Chl type during folding, segregating the preferred Chl to the correct binding site.

Brainstem and Spinal Arachnoiditis Ossificans Associated With Neurocysticercosis: A Case Report.

Arachnoiditis ossificans (AO), a very rare entity that can cause severe neurological deficit, is associated with an inflammatory response and compressive effect on the spinal cord. A 65-year-old woman with diagnosis of arachnoiditis ossificans, who had a past medical history of neurocysticercosis diagnosed eight years before the actual onset that was accompanied by obstructive hydrocephalus and required bilateral ventriculoperitoneal shunts, presented with lower limb paresis. The spinal CT reported large calcified subdural spinal plaques. She was treated with high-dose steroids with subsequent improvement of the clinical manifestations. Spinal neurocysticercosis is a rare manifestation of this disease, although the Mexican population is especially prone to it, due to the endemic presence of this entity, it can provoke spinal arachnoiditis. We conclude that the chronic inflammation of the spinal meninges induced by the cysticercosis could encourage the arachnoid cells to go through osteoblastic metaplasia with consequent production of thick calcium deposits, such as those found in AO. Thus it may be associated with AO. We present, to our knowledge, the first patient with AO-associated neurocysticercosis.

Ring-Enhancing Progressive Multifocal Leukoencephalopathy Mimicking Glioma in a Presumed Immunocompetent Patient With a History of Multiple Sclerosis: A Case Report and Review of the Literature.

The differential diagnoses of ring-enhancing lesions of the brain parenchyma is broad, but complete ring-enhancing lesions often indicate a neoplastic or infectious process. We present a case of a 70-year-old female with a history of multiple sclerosis (MS) who was not on current disease-modifying therapy (DMT) and was found to have a ring-enhancing lesion that mimicked a high-grade glioma. The patient underwent gross total resection, and histopathologic and molecular analysis revealed a diagnosis of progressive multifocal leukoencephalopathy (PML). A subsequent medical workup on the patient was unrevealing aside from mild lymphopenia. This is a unique case that highlights both an unusual clinical presentation and radiographic appearance of PML. There is a known associated increased risk of PML with the use of some DMTs for MS. However, this case raises the question of the possibility of developing PML years after interferon beta-1a therapy in a patient without overt immunosuppression.